This proposal is directed at characterizing the role of vasoactive agents, particularly prostaglandins, in fetal cardiocirculatory homeostasis. Evidence has emerged from our own and other laboratories suggesting strongly that the prostaglandins play a key role in the dramatic events that occur in the transition in the postnatal period from fetal to adult circulatory pathways. In particular, major clinical implications exist concerning the role of prostaglandins in controlling the circulation of the ductus arteriosus. Techniques have been developed in our laboratory that allow direct observations chronically of the ductal caliber in situ. Thus, we propose to study the undisturbed fetal and neonatal lamb to evaluate the effects of prostaglandins and their inhibitors on the hemodynamics of the ductus arteriosus, as well as the interaction between these stimuli, other vasoactive agents, and the autonomic nervous system. Chronic studies are aimed also at examining the role of the unique blood flow patterns in the perinatal period in influencing ductal patency or contriction, changes in organ blood flows induced by altering ductal caliber, and the influence of altering the maternal prostaglandin milieu on the fetal circulation. Investigations are outlined of the isolated ductus arteriosus to evaluate the influence of lung-derived vasoactive substances on ductus myotropic responses and to assess the possible participation of second messenger systems, i.e., the cyclic nucleotides in ductal constriction and dilatation. The mechanisms underlying the physiological behavior of the ductus arteriosus will also be explored biochemically in isolated systems by age relating the ability of the lungs, the ductus arteriosus, and other fetal, newborn, and adult blood vessels to generate terminal prostaglandins. Lastly, studies are proposed of newborn lamb renal function seeking to define potential age-dependent nephrotoxicity caused by inhibitors of prostaglandin synthesis used clinically in pre-term infants.